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Title: Domain disruptions of individual 3B proteins for foot-and-mouth disease virus do not alter growth in cell culture nor virulence in cattle

Author
item Pacheco Tobin, Juan
item PICCONE, MARIA - University Of Connecticut
item Rieder, Aida - Elizabeth
item Pauszek, Steven
item Borca, Manuel
item Rodriguez, Luis

Submitted to: Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/27/2010
Publication Date: 6/30/2010
Citation: Pacheco Tobin, J., Piccone, M.E., Rieder, A.E., Pauszek, S.J., Borca, M.V., Rodriguez, L.L. 2010. Domain disruptions of individual 3B proteins for foot-and-mouth disease virus do not alter growth in cell culture nor virulence in cattle. Virology. DOI: 10.1016/j.virol.2010.05.036.

Interpretive Summary: Foot-and-mouth disease (FMD) is a highly contagious viral disease of cattle, pigs, sheep, goats, and wild cloven-hoofed animals. The disease is characterized by fever and vesicular lesions of the epithelium of the mouth, tongue, feet, and teats. The FMD virus (FMDV) requires a small viral protein (3B) that is linked to the viral RNA to replicate. Interestingly unlike other members of its family that encode a single copy of 3B, FMDV encodes three copies of this protein that are similar but not identical in amino-acid sequence. There are no reports of naturally occurring FMDV strains with fewer than three copies of 3B, suggesting a critical role for each of them. In order to examine the role of 3B in FMDV pathogenesis in cattle, viruses containing disrupted or lacking one of their 3B proteins were derived in the laboratory. Mutant viruses had growth characteristics similar to the parental virus in various cell lines. Furthermore, cattle infected by aerosol exposure with mutant viruses harboring insertions or deletions in the 3B proteins developed clinical disease similar to that caused by the parental virus. These results indicate that 3B function is redundant and it is possible to create viruses with reduced number of 3B proteins. This information is being applied to the rational design of FMDV vaccines.

Technical Abstract: Picornavirus RNA replication is initiated by a small viral protein primer, 3B (also known as VPg), that is covalently linked to the 5’RNA of the viral genome. In contrast to other picornaviruses that encode a single copy of 3B, foot-and-mouth disease virus (FMDV) encodes three copies of 3B that are similar but not identical in amino-acid sequence. Despite the fact that not all three copies of FMDV 3B are needed for viral replication, there are no reports of naturally occurring FMDV strains with fewer than three copies of 3B, suggesting a critical role for each of them. In order to examine the role of 3B peptides in FMDV pathogenesis in cattle, viruses containing disrupted native sequence or deletion of one of their three 3B proteins were derived from a FMDV A24 Cruzeiro full-length cDNA infectious clone. Despite harboring severe domain disruptions or lacking one of their 3B proteins, mutant viruses had growth characteristics similar to the parental virus in hamster, bovine and porcine cell lines. RNA synthesis and protein cleavage processes were not significantly affected in these mutant viruses. Cattle infected by aerosol exposure with mutant viruses harboring insertions or deletions in the 3B proteins developed clinical disease similar to that caused by the parental A24 Cruzeiro. Therefore, severe domain disruption or deletion of individual 3B proteins in FMDV do not affect the virus’ ability to replicate in vitro and cause clinical disease in cattle.